The major objectives of the proposed research are to elucidate the cause of and to develop effective treatments for calcareous renal stones and bone disease. The cause for nephrolithiasis will be sought both in vitro and in vivo, from examination of physicochemical factors concerned with stone formation (nucleation, crystal growth, aggregation and epitaxy), as well as elucidation of underlying metabolic defect (e.g., hypercalciuria, hyperuricosuria, hyperoxaluria). Concurrent with these studies of pathogenetic mechanism, the proposed research will seek to develop rational mode of therapy. The action of various drugs (e.g., thiazides and phosphates) will be delineated objectively on the basis of their effects on nucleation, crystal growth, aggregation or epitaxy. Optimal uses of drugs will be developed on the basis of their ability to "correct" the underlying metabolic disorder (e.g., cellulose phosphate for absorptive hypercalciuria and thiazides for renal hypercalciuria). Factors concerned with the synthesis of 1,25-dihydroxycholecalciferol will be examined in man. An attempt will be made to better define its therapeutic indications by examining its effect on jejunal Ca absorption and elucidating the physical chemistry of soft tissue calcification.